The long term goal of this BRP remains the development of a clinically useful retinal prosthesis for patients blinded by outer retinal degenerations, such as retinitis pigmentosa and macular degeneration. In the first funding period, we not only completed all our aims, including the creation and long-term animal testing of a fully functional 16 electrode prototype system, but we also successfully implanted six subjects with this device, the world's only active long-term retinal prostheses, in a FDA-approved study. In the next phase of our research, we will: 1. Complete the development of a versatile epiretinal prosthesis (A-60), test its reliability and safety in animals, and implant it in humans. Through a unique pairing of electrophysiological recordings in animal models of retinal degeneration and clinical experiments in human subjects, we will use this device to: 2. Determine electrode array design specifications, compare epiretinal and subretinal configurations, determine electrical stimulation algorithms to maximize spatial resolution and brightness range, and determine the need for eye tracking in a next generation retinal prosthesis. Finally, we will 3. Design, test, and implant in humans a next generation retinal prosthesis to restore useful vision. To accomplish these challenging but attainable goals, this proposal brings together a sophisticated multidisciplinary team including a non-profit foundation (AMF, with 30+ years of implantable device expertise and specialized facilities), three academic institutions (USC for human clinical testing and patch-clamp physiology; Doheny Eye Institute for surgical and large animal studies; and The Salk Institute for multi- electrode physiology) and a private company (Second Sight for engineering research and development, manufacturing, and regulatory). Our continued collaboration with engineers, scientists and physicians will allow us to achieve our goal of providing many blind patients with an important therapy where none currently exists.